Local delivery of therapeutics to the site of action in the body is often desired. For example, bronchodilator drugs are most effective when inhaled directly into the lungs, avoiding systemic circulation which can lead to rapid metabolism of compounds as well as effects at tissues other than the target sites. In the same way, targeted or focal delivery of cells, as part of a therapeutic regimen, would be useful to avoid potential side effects of cell treatment as well as metabolism by the body.
Accordingly, focal delivery of cells in the human body has been an active area of research. Cells have been explored as means of gene transfer to the brain, instead of viral vectors (Taylor, R., 1997 Neuromuscul. Disord., 7:343-351); neural precursor cells containing genes encoding deficient enzymes were transplanted into mouse models of neurodegenerative disease. Engineered urothelial cells have also been locally implanted to produce a functional neo-organ (Yoo, J. J. and A. Atala, 1997 J. Urol., 158:1066-1070). Encapsulated genetically engineered cells that continuously released ciliary neurotrophic factor have also been tested in humans and animals (Tan, S. A. et al., 1996 Cell Transplant., 5:577-587).
Paramagnetic particles and paramagnetic techniques are used in medicine in a variety of ways. For example, paramagnetic contrast media have been described by Catalano, C. et al., 1995 Radiol. Med., 89:825-830; Jackler, R. K. et al., 1990 Otolaryngol. Head Neck Surg., 102:70-77; and Bonnet, P. A. et al., 1990 Magn. Reson. Imaging, 8:71-77. A hepatocyte-specific contrast media that allows for specific imaging of hepatitis has also been described by Tanimoto, A. et al., 1993 J. Magn. Reson. Imaging, 3:786-793. Paramagnetic substances are also used in analytical chemical assays.
Internalized magnetic particles have also been used to study inflammation. For example, Yeh et al., 1993 MRM, 30:617-625 and 1995 MRM, 33:200-208, demonstrated that rat T-cells that have internalized dextran-coated iron oxide particles can be used to identify areas of inflammation by magnetic resonance imaging. Similarly, Krieg et al., 1995 Magn. Reson. Imagine, 13:393-400, demonstrated that neutrophils that had previously phagocytosed polystyrene-embedded magnetite micro crystals could be used to identify sites of inflammation on T2-weighted magnetic resonance images.
It has now been found that magnetic particles can be used in the focal delivery of cells. In the present invention, a new method for targeted delivery of cells is provided using magnetic particle-containing cells and a magnetic field which ensures adequate attachment of cells to the target tissue. Once attached, cells and their products are available for local activity.